SPIRIT study: switching to emtricitabine/rilpivirine/tenofovir df (FTC/RPV/TDF) single-tablet regimen (STR) from a ritonavir-boosted protease inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIS) maintains HIV suppression and improves seru

Background: Antiretroviral regimen simplification improves both quality of life, and long-term medication adherence while reducing the risk of HIV virologic failure (VF) and long-term drug-related toxicities. FTC/RPV/TDF is a well-tolerated, once daily STR treatment option. This is the first study to evaluate the efficacy and safety of switching from boosted Protease Inhibitor (PI) based HAART to a simplified regimen of FTC/RPV/TDF STR.
Methods: A randomized, open-label, multi-center, international, 48 week study to evaluate the safety and efficacy of switching from ritonavir-boosted PI regimens to FTC/RPV/TDF in virologically-suppressed (HIV RNA< 50 copies/mL), HIV-1 infected subjects. Participants were randomized 2:1 to switch to FTC/RPV/TDF or maintain their current PI-based regimen. The primary endpoint was non-inferiority (12% margin) of FTC/RPV/TDF relative to PI-based regimens in maintaining plasma HIV-1 RNA< 50 copies/mL at Week 24 by Snapshot analysis. Changes in serum lipids from baseline were evaluated.
Results: A total of 476 subjects were randomized and received at least 1 dose of study drug (317 FTC/RPV/TDF; 159 PI). Baseline characteristics were similar (table 1). Switching to FTC/RPV/TDF was non-inferior to maintaining a ritonavir-boosted PI regimen (93.4% versus 89.9%) at Week 24 for HIV RNA< 50 copies/mL (95% CI [-2.0%, 8.9%]). Fewer subjects in the FTC/RPV/TDF arm than the PI arm had virologic failure by Snapshot, defined as HIV RNA≥50 copies/mL at Week 24 or discontinuations of study drug with HIV RNA≥50 copies/mL (1.3% vs 5.0%). Two subjects in the FTC/RPV/TDF arm had emergent resistance and one in the PI arm. Overall total cholesterol, LDL, and triglycerides decreased to a greater extent among FTC/RPV/TDF than PI recipients (table 2).


 FTC/RPV/TDFPI
Males (%)86.190.6
Black or African Heritage (%)19.213.8
Age (mean, years)4143
CD4 (mean, cells/mm3)576600
[Baseline Demographics]




 BaselineMean Change at Week 24 
 FTC/RPV/TDFPIFTC/RPV/TDFPIp value
Total Cholesterol (mg/dL)192194-25-1<0.001
LDL (mg/dL)121124-160<0.001
Triglycerides (mg/dL)163173-533<0.001
HDL (mg/dL)5350-4-1<0.001
Total Cholesterol/HDL3.864.08-0.270.08<0.001
[Fasted Serum Lipids and Change from Baseline at We]


Conclusions: Switching to the FTC/RPV/TDF STR from a ritonavir-boosted PI regimen in virologically-suppressed, HIV-1-infected participants maintains virologic suppression with low risk of virologic failure while improving total cholesterol, LDL, and triglycerides.

F. Palella1, P. Tebas2, B. Gazzard3, P. Ruane4, D. Shamblaw5, J. Flamm6, M. Fisher7, J. van Lunzen8, R. Ebrahimi9, K. White9, B. Guyer9, H. Graham9, T. Fralich9
1Northwestern University, Feinberg School of Medicine, Chicago, United States, 2University of Pennsylvania, Division of Infectious Diseases, Clinical Trials Unit, Philadelphia, United States, 3Chelsea and Westminster Hospital Foundation Trust, London, United Kingdom, 4Peter J. Ruane, MD, Inc., Los Angeles, United States, 5La Playa Medical Group and Clinical Research, San Diego, United States, 6Kaiser Permanente, Sacramento, United States, 7Brighton and Sussex University Hospitals, Brighton, United Kingdom, 8University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 9Gilead Sciences, Foster City, United States